This invention relates to the preparation of 1S,4S- and 1R,4R-2-alkyl-2,5-diazabicyclo[2.2.1]-heptane intermediates having utility in the preparation of antibacterial quinolones such as those disclosed in U.S. Pat. No. 4,775,668.
A method for the synthesis of 2,5-diazabicyclo[2.2.1]heptanes has been described by Portoghese et al., J. Org. Chem., 31, 1059 (1966). According to this method, hydroxy-L-proline is transformed into tritosylhydroxy-L-prolinol which is first reacted with benzylamine and then with hydrogen iodide, phosphorus, and acetic acid to form N-benzyl-2,5-diazabicyclo[2.2.1]heptane dihydroiodide. U.S. Pat. No. 3,947,445 follows a similar procedure and then converts the dihydroiodide through a three step procedure into 2-methyl-2,5-diazabicyclo [2.2.1 ]heptane.
In our prior copending application, Ser. No. 50,423, filed May 11, 1989, we describe another method for the preparation of said optically active 2,5-diaza-2-alkylbicyclo [2.2.1]heptanes of the formula (IX) below from trans-4-hydroxy prolines of the formula (I) below.